Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC. METHODS: Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups. RESULTS: Among 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS: Only patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

Prognostic impact of peritoneal washing cytology in patients with biliary tract cancer.

PURPOSE: To elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC). METHODS: Clinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis. RESULTS: Among the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19-9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively). CONCLUSION: Patients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

PURPOSE: The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. METHODS: Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. RESULTS: The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). CONCLUSIONS: Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Long-term outcomes of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact: Results from a phase II trial.

BACKGROUND/PURPOSE: This study reports the long-term results of a phase II trial evaluating the clinical efficacy of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact (BRPC-A). METHODS: A multicenter, single-arm, phase II trial was conducted. Patients received six cycles of GAS and patients without progressive disease were intended for R0 resection. RESULTS: Of the 47 patients, 45 (96%) underwent pancreatectomy. At the time of this analysis, all patients were updated with no loss to follow-up. A total of 30 patients died, while the remaining 17 patients were followed for a median of 68.1 months. The updated median overall survival (OS) was 41.0 months, with 2- and 5-year OS rates of 68.0% and 44.6%, respectively. Multivariate analysis in the preoperative model showed that a tumor diameter reduction rate ≥10% and a CA19-9 reduction rate ≥95% after neoadjuvant chemotherapy remained independently associated with favorable survival. In the postoperative multivariate model, no lymph node metastasis, no major surgical complications, and completion of adjuvant chemotherapy were independently associated with improved OS. CONCLUSIONS: This long-term evaluation of the neoadjuvant GAS trial demonstrated the high efficacy of the regimen, suggesting that it is a promising treatment option for patients with BRPC-A.

Optimal Lymphadenectomy in Patients with Well-Differentiated Nonfunctioning Pancreatic Neuroendocrine Neoplasms.

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms.

Increased plasma miR-370-3p expression in poor-outcome patients with pancreatic ductal adenocarcinoma.

OBJECTIVE: To determine whether circulating microRNAs (miRNAs) can be used as prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with PDAC (N = 120) who underwent surgical resection at Hiroshima University Hospital between November 2006 and January 2020 were enrolled in this study and grouped based on their overall survival (OS) into two groups: favorable prognosis group (F group; OS ≥ 18 months) and unfavorable prognosis group (U group; OS < 18 months). Blood plasma samples were collected prior to surgery. To identify candidate prognostic miRNAs, next-generation sequencing (NGS) analysis was used to evaluate the expression levels of miRNAs in seven of the plasma samples. Using quantitative real-time PCR (qRT-PCR), the expression levels of the selected miRNAs were determined in the remaining 113 patient plasma samples, and the relationship between miRNA expression and survival was statistically evaluated. RESULTS: NGS analysis and qRT-PCR revealed significantly upregulated plasma miR-370-3p expression in the U group compared to that in the F group (p = 0.028 and p = 0.005, respectively). Moreover, miR-370-3p expression and lymph node metastasis showed a statistically significant association (p = 0.028). In a multivariate analysis of OS and recurrence-free survival (RFS), the upregulation of miR-370-3p expression in plasma was identified as an independent risk factor for poor OS (HR2.13, p = 0.004) and RFS (HR1.84, p = 0.015). CONCLUSIONS: Plasma miR-370-3p expression upregulation correlates with poor prognosis in patients with PDAC.

Difficulty of adjuvant chemotherapy administration in patients with biliary tract cancer.

PURPOSE: This study aimed to elucidate the difficulty of adjuvant chemotherapy administration in patients with biliary tract carcinoma (BTC). METHODS: Clinical data of patients with BTC who underwent curative-intent surgery were retrospectively analyzed. The eligible patients were stratified into two groups according to the presence or absence of adjuvant chemotherapy administration (adjuvant and non-adjuvant groups), and the clinicopathological features were compared between the two groups. The ratios of adjuvant chemotherapy administration were investigated in each surgical procedure. Independent factors associated with no administration of adjuvant chemotherapy were analyzed using multivariate analyses. RESULTS: Among 168 eligible patients, 141 (83.9%) received adjuvant chemotherapy (adjuvant group), while 27 (16.1%) did not (non-adjuvant group). The most common surgical procedure was pancreaticoduodenectomy in the adjuvant group, and it was hepatectomy with extrahepatic bile duct resection (BDR) in the non-adjuvant group, respectively. The rate of no adjuvant chemotherapy was significantly higher in patients who underwent hepatectomy with BDR than in those who underwent other surgeries (p < 0.001). The most common cause of no adjuvant chemotherapy was bile leak in 12 patients, which occurred after hepatectomy with BDR in ten patients. Multivariate analyses revealed that hepatectomy with BDR and preoperative anemia were independently associated with no adjuvant chemotherapy (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Hepatectomy with BDR and subsequent refractory bile leak can be the obstacle to adjuvant chemotherapy administration in patients with BTC.

Prognostic factor in patient with recurrent pancreatic adenocarcinoma.

PURPOSE: To elucidate prognostic factors for post-recurrence survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients who underwent curative-intent surgery for PDAC between January 2014 and May 2020 were identified. Among them, patients who had postoperative recurrences and received chemotherapy were retrospectively investigated. Independent prognostic factors for survival after recurrence were investigated using multivariate analyses. Eligible patients were divided into two groups according to the presence or absence of the identified prognostic factors, and survival times after recurrence were compared. RESULTS: Eighty-four patients with recurrent PDAC were included. Multivariate analysis showed that red blood cell (RBC) transfusion (HR, 2.80; p = 0.0051), low albumin level (HR, 1.84; p = 0.0402), and high carbohydrate antigen 19-9 (CA19-9) level at recurrence (HR, 2.11; p = 0.0258) were significant predictors of shorter survival after recurrence. The median survival times after recurrence in the transfusion and non-transfusion groups were 5.5 vs. 18.1 months (p < 0.0001), respectively; those in the low and normal albumin groups were 10.1 vs. 18.7 months (p = 0.0049), and those in the high and normal CA19-9 groups were 11.5 vs. 22.6 months (p = 0.0023), respectively. CONCLUSIONS: RBC transfusion, low albumin, and high CA19-9 levels at recurrence negatively affected survival after recurrence in patients with PDAC.

Prognostic impact of lung recurrence in patients with biliary tract cancer.

PURPOSE: This study aimed to evaluate the prognostic impact of the initial recurrence site following resection for biliary tract carcinoma (BTC), focusing on lung recurrence. METHODS: The clinical data of patients with recurrent BTC who underwent curative intent surgery between March 2009 and December 2021 were retrospectively analyzed. The prognosis of patients with recurrent BTC was investigated in each recurrence site. Eligible patients were classified into two groups according to lung or non-lung recurrence. Clinicopathological factors, survival after recurrence, and overall survival were compared between the two groups. Independent factors associated with survival after recurrence were investigated using multivariate analysis. RESULTS: Of 119 patients, the initial recurrence site was local in 26 (21.8%) patients, liver in 19 (16.8%), peritoneum in 14 (11.8%), lymph node in 12 (10.1%), lung in 11 (9.2%), multiple organs in 32 (26.9%), and others in 5 (4.2%). The survival period after recurrence in patients with lung recurrence was significantly longer than those in patients with other six recurrence patterns. The median survival after recurrence was 34.3 and 9.3 months in lung recurrence and non-lung recurrence groups, respectively (p < 0.0001); that after initial surgery was 50.8 and 26.4 months, respectively (p = 0.0383). Multivariate analysis revealed that lung recurrence and normal albumin level at recurrence were independently associated with survival after recurrence (Hazard Ratio (HR), 0.291; p = 0.0128; HR, 0.476; p = 0.00126, respectively). CONCLUSIONS: Survival period after recurrence was significantly longer in patients with lung recurrence.

Surgical resection for liver recurrence after curative resection of pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to evaluate the clinical significance of surgical resection for liver recurrence in patients with curatively resected pancreatic ductal adenocarcinoma. METHODS: The medical records of patients with a liver recurrence after undergoing curative pancreatectomy for pancreatic ductal adenocarcinoma were retrospectively reviewed. Clinicopathological and prognostic factors were analyzed, as was the clinical impact of surgical resection for liver recurrence. RESULTS: Overall, 502 patients underwent curative pancreatic ductal adenocarcinoma resection. Of the 311 patients with recurrence after curative pancreatectomy, 71 (23%) had an initial recurrence in the liver, with 35 having solitary recurrence (11%). Patients with solitary, two or three, or more than four recurrences had median overall survival times of 28.5, 18.0, and 12.2 months, respectively (p < 0.001). Surgical indications for liver recurrence in our institution included solitary tumor, good disease control under chemotherapy after recurrence for > 6 months, and sufficient remnant liver function. Ten patients who met our institutional policy inclusion criteria underwent liver resection. Among 35 patients with initially solitary liver recurrence, those who underwent liver resection outlived those who did not (57.6 months vs. 20.1 months, p < 0.001). In multivariate analysis of overall survival, solitary liver recurrence and liver resection were independent favorable prognostic factors in patients with initial liver recurrence. CONCLUSION: In selected patients with solitary liver recurrence after curatively resected pancreatic ductal adenocarcinoma, liver resection may be a treatment option.

Hepatic artery resection in distal cholangiocarcinoma.

PURPOSE: This study aimed to elucidate the safety and oncological outcomes of surgery with hepatic artery resection (HAR) for patients with distal cholangiocarcinoma. METHODS: The clinical data of patients with distal cholangiocarcinoma who underwent curative intent surgery at Hiroshima University between March 2009 and January 2021 were retrospectively analyzed. Eligible patients were classified according to the presence or absence of HAR (HAR and non-HAR group), and clinicopathological features and disease-free survival rates were compared between the two groups. RESULTS: Among the 60 patients analyzed, eight patients had received HAR, and the remaining 52 patients had not. The rate of portal vein resection, T stage, and the number of metastasized lymph nodes in the HAR group were significantly greater than those in the non-HAR group (p < 0.001, p = 0.00695, and p = 0.0480, respectively). Postoperative severe complication was confirmed in one patient, and there were no in-hospital deaths in the HAR group. Seven of 8 patients in the HAR group showed recurrence during follow-up, and of those, six patients showed early recurrence within 1 year postoperatively. The disease-free survival time in the HAR group was significantly shorter than that in the non-HAR group (median: 7.4 m vs. 34.2 m, respectively) (p < 0.001). Multivariate analysis revealed that lymph node metastasis and HAR were significant risk factors for predicting the adverse disease-free survival time (hazard ratio (HR), 3.21; p = 0.0142; HR, 4.47; p = 0.0346, respectively). CONCLUSIONS: Patients with distal cholangiocarcinoma who underwent surgery with HAR tended to show early recurrences, although HAR could be performed safely.

Pathologic complete response following FOLFIRINOX and olaparib treatment for hepatic metastasized pancreatic ductal adenocarcinoma with a germline BRCA mutation.

A 47-year-old female who was previously treated for BRCA1 germline mutant breast cancer presented with increasing back pain. Radiological and pathological investigations led to the diagnosis of pancreatic ductal adenocarcinoma with multiple hepatic metastases. Serum carbohydrate antigen 19-9 levels were highly elevated at 14,784 U/mL (normal, < 37 U/mL). After nine cycles of FOLFIRINOX treatment, radiological findings revealed remarkable shrinkage of the primary pancreatic tumor, disappearance of hepatic metastases, and normalized levels of carbohydrate antigen 19-9 levels. Because of increased neuropathy following FOLFIRINOX treatment, the patient was switched to maintenance olaparib treatment. Ten months later, her radiological response and normalized carbohydrate antigen 19-9 levels were stable. After staging laparoscopy, the patient underwent laparoscopic distal pancreatectomy as a conversion surgery. Histopathological examination revealed no signs of residual adenocarcinoma in the resected pancreatic specimens, which was diagnosed as a pathological complete response. The patient recovered without complications. Adjuvant olaparib treatment was administered with no signs of recurrence at 7 months after surgery. In conclusion, a pathologic complete response after FOLFIRINOX and olaparib maintenance treatment in hepatic metastasized pancreatic ductal adenocarcinoma is extremely rare. These bridging treatments may contribute to increased surgical resection rates and improved survival rates.

Prognostic impact of postoperative infection in patients with pancreatic cancer: A multicenter cohort study.

BACKGROUND: Postoperative infection after pancreatectomy in patients with pancreatic cancer often leads to poor prognosis. The aim of this study was to determine the prognostic effect of postoperative infection in patients with pancreatic cancer. METHODS: A multicenter cohort study was performed using a common database of patients with pancreatic cancer who underwent curative pancreatic resections between April 2013 and March 2015 at 15 high-volume centers in Japan. The rate of postoperative infection was determined, and patient demographic characteristics, clinicopathologic factors, and prognostic factors for overall survival were analyzed. RESULTS: Of the 462 eligible patients who underwent curative pancreatectomy, postoperative infection occurred in 141 patients (31%), including 114 surgical site infections (25%), 50 remote infections (11%), and 23 combined infections (5%). Risk factors for postoperative infection included high body mass index, nondiabetes, and longer operation time. In the survival analysis, patients with postoperative infection had significantly worse overall survival than patients without postoperative infection. The median survival times were 21.9 and 33.0 months (P = .023), respectively, for patients with and without postoperative infection. According to the multivariate analysis for overall survival, lack of adjuvant therapy (P = .002), but not postoperative infection (P = .829), predicted poor prognosis. The multivariate analysis revealed that postoperative infection (P < .001) was an independent risk factor for lack of adjuvant therapy. CONCLUSION: Postoperative infection in patients with pancreatic cancer may indirectly worsen the prognosis by preventing timely adjuvant therapy.

A case of unresectable locally advanced intrahepatic cholangiocarcinoma that achieved pathological complete response after gemcitabine and S1 chemotherapy.

The standard chemotherapy for patients with unresectable cholangiocarcinoma is gemcitabine plus cisplatin, and gemcitabine plus S-1 (GS) chemotherapy is also reported to have similar effectiveness in Japan. However, the response rates of these two chemotherapies were modest, and no patients with intrahepatic cholangiocarcinoma (ICC) have shown a pathological complete response (pCR) following these chemotherapies. We report here the first case of an initially unresectable locally advanced ICC that achieved pCR following GS chemotherapy.

Mesenteric approach in pancreas-preserving partial duodenectomy for aortic graft-duodenal fistula: a case report.

An aortic graft-duodenal fistula commonly requires graft replacement and duodenectomy. However, the appropriate surgical approach to the duodenum with aortic graft fistula remains unclear. Herein, we describe the case of an 85-year-old male patient who underwent a pancreas-preserving partial duodenectomy using the mesenteric approach for aortic graft-duodenal fistula. The patient presented with hemorrhagic shock and duodenal bleeding 2 years after undergoing open aortic graft replacement. He first underwent emergent endovascular aortic repair with an artificial vascular graft to achieve hemostasis. Although his general condition stabilized following endovascular treatment, duodenal endoscopy revealed an aortic graft-duodenal fistula, exposing the artificial vascular graft via the third portion of the duodenum. As the radical treatment for aortic graft-duodenal fistula, open graft replacement and pancreas-preserving partial duodenectomy were performed using the mesenteric approach which helps to divide the pancreas and duodenum. The patient recovered without any major complications, such as postoperative pancreatic fistula, and was discharged. In conclusion, the mesenteric approach in partial duodenectomy for aortic graft-duodenal fistula could be safely performed. This procedure is useful to approach the duodenum fixed by fistula formation, which may help reduce intraoperative blood loss, operative time, and surgical invasiveness.

Clinicopathological features of gastric cancer after pancreaticoduodenectomy: reporting of three institutional cases and review of the global literature.

PURPOSE: Gastric cancer after pancreaticoduodenectomy was firstly reported in 1995, and the number of reports about this topic has increased in the past years. This review aimed to elucidate the clinicopathological features of this disease. METHODS: Data for 32 cases were obtained using literature search, and three cases in our institution were added. RESULTS: Twenty cases were reported from Japan, and fifteen cases were from the Western countries (Germany: 1 case, France: 2 cases, USA: 12 cases). In Japanese and the Western cases, the most dominant indication for pancreaticoduodenectomy was distal bile duct cancer and pancreatic ductal adenocarcinoma, respectively. The most frequently applied procedure of pancreaticoduodenectomy was pylorus-preserving pancreatoduodenectomy with pancreaticogastrostomy and pancreaticoduodenectomy with pancreaticojejunostomy, respectively. The median length of time interval from pancreaticoduodenectomy to GC detection tended to be shorter in the Japanese cases (61.5 months vs. 115 months). Of all cases, thirteen (37.1%) patients with gastric cancer showed no abdominal symptoms, and eight were diagnosed at regular gastroscopy. Surgical gastrectomy was performed in 30 patients, and among them, concomitant pancreatectomy was performed in six patients. Four patients received reanastomosis of remnant pancreas using pancreaticojejunostomy. Twenty-two (73.3%) patients had undifferentiated carcinomas, and stage 1, 2, 3, and 4 cancer was identified in 14, six, six, and four patients, respectively. All eight patients who had received routine gastroscopy were T1N0M0 stage 1. CONCLUSION: Gastric cancers after pancreaticoduodenectomy including newly reported Japanese cases and our institutional cases were reviewed to make Japanese studies available to a broader scientific audience. Further investigation is necessary to elucidate the most important carcinogens among the various potential local and systemic factors.

Prognosis following an extended duration of adjuvant gemcitabine plus S-1 chemotherapy in patients with pancreatic ductal adenocarcinoma: Analysis using inverse probability of treatment weighting.

BACKGROUND/PURPOSE: The aim of this study was to assess whether the duration of adjuvant gemcitabine plus S-1 (GS) chemotherapy has any effect on survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Of the 290 patients who received adjuvant GS chemotherapy, 100 (34%) received the standard duration (20-29 weeks) and 190 (66%) received an extended duration (≥30 weeks). To reduce selection bias, the prognostic impact (recurrence-free survival [RFS] and overall survival [OS]) based on the duration of adjuvant GS chemotherapy was analyzed using inverse probability of treatment weighting (IPTW). Moreover, to reduce immortal time bias, time-dependent multivariate analyses in which implementation of adjuvant GS chemotherapy was treated as time-varying covariate was also performed. RESULTS: Extended duration of adjuvant GS chemotherapy was significantly correlated with prolonged RFS (P < .001) and OS (P < .001) after IPTW adjustment. Time-dependent multivariate analyses revealed that extended duration of adjuvant GS chemotherapy was an independent prognostic factor for prolonged RFS (hazard ratio [HR], 0.58, P = .002) and OS (HR, 0.56, P = .005). CONCLUSION: Extended duration (≥30 weeks) of adjuvant GS chemotherapy in patients with PDAC was associated with an improved prognosis. These findings warrant a further prospective trial on PDAC to investigate the survival benefit of extended adjuvant chemotherapy.

Preoperative risk factors for positivity of peritoneal lavage cytology in patients with pancreatic ductal adenocarcinoma in the era of neoadjuvant therapy.

BACKGROUND: The preoperative risk factors for positive peritoneal lavage cytology (CY) are unknown, especially in patients who received neoadjuvant therapy. In addition, the optimal indications for staging laparoscopy (SL) are still unclear. The aim of this study was to investigate the preoperative risk factors of CY positivity in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection and to determine the optimal indications for SL. METHODS: We retrospectively analyzed 493 patients with PDAC, including 356 treated with upfront surgery and 137 treated with neoadjuvant chemotherapy (NAC). The preoperative risk factor for CY positivity was investigated along with stratification according to NAC. RESULTS: Among the 493 patients, 36 (7.3%) were CY-positive. The CY-positive frequency in patients who received and did not receive NAC was 9 (6.6%) and 27 (7.6%), respectively. In the multivariate analyses, no independent preoperative predictive factor was found in patients who received NAC, whereas body and tail PDAC were identified as an independent risk factor for CY positivity in patients who did not receive NAC. CONCLUSIONS: The preoperative risk factors of CY-positive PDAC are body and tail PDAC in 356 patients who did not receive NAC. However, there is no useful predictive factor for CY positivity in patients treated with NAC. Based on these results, it was difficult to determine the optimal indication for SL especially in NAC cases.

Impact of disintegrin and metalloproteinase domain-containing protein 12 on pancreatic ductal adenocarcinoma treated with surgical resection and perioperative chemotherapy.

BACKGROUND/OBJECTIVES: A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) has been reported to influence tumor progression and chemosensitivity in human cancers. We assessed the prognostic impact of ADAM12 and its predictive value for neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection. METHODS: ADAM12 expression was immunohistochemically examined in 428 patients with PDAC who underwent surgical resection. The association of ADAM12 expression with clinicopathological factors and survival was also analyzed. RESULTS: Patients with high ADAM12 expression exhibited significantly shorter median disease-free survival (DFS) (high ADAM12: 17.8 vs. low ADAM12: 37.9 months; P < 0.001) and overall survival (OS) (high ADAM12: 33.1 vs. low ADAM12: 65.0 months; P < 0.001). A multivariate analysis revealed that high ADAM12 expression was an independent risk factor for poor DFS (P < 0.001) and OS (P < 0.001) in all eligible patients. Of 100 patients who received neoadjuvant chemotherapy (NAC), high ADAM12 expression was significantly associated with poor DFS in a subset of patients treated with the nab-paclitaxel (PTX) neoadjuvant regimen (P = 0.03), whereas the prognostic value of ADAM12 was not evident in patients not treated with nab-PTX (P = 0.12). CONCLUSIONS: A negative prognostic value of high ADAM12 expression was observed in patients with PDAC treated with surgical resection, which was enhanced in patients treated with NAC, including nab-PTX. These results suggested that ADAM12 expression can predict nab-PTX chemosensitivity in PDAC and reflect PDAC progression.

Long-term survival after distal pancreatectomy with celiac axis resection and hepatic artery reconstruction in the setting of locally advanced unresectable pancreatic cancer.

The long-term survival of patients with locally advanced, unresectable pancreatic cancer is extremely poor. We present our experience with a 67-year-old woman who had a 40-mm mass in the body of the pancreas. Tumor infiltration reached the gastroduodenal artery, celiac artery, common hepatic artery, and splenic artery. After 10 courses of FOLFIRINOX, 2 courses of gemcitabine plus nab-paclitaxel, and 6 courses of gemcitabine alone, we performed distal pancreatectomy with celiac axis resection and hepatic artery reconstruction. The bifurcation of the gastroduodenal artery and the proper hepatic artery had to be resected, after which we created 2 anastomoses: proper hepatic-to-middle colic artery, and second jejunal-to-right gastroepiploic artery. Histopathologic examination revealed an Evans grade IIb histologic response to prior treatment and verified the R0 resection status. The patient was discharged on postoperative day 30 after treatment of a grade B pancreatic fistula and is still alive, without recurrence, more than 5 years after initiation of treatment. This patient with locally advanced, unresectable pancreatic cancer achieved long-term survival through perioperative multidisciplinary treatment, including distal pancreatectomy with celiac axis resection and hepatic artery reconstruction. This aggressive procedure could be a treatment option for patients with locally advanced, unresectable pancreatic cancer.